Architectural Basis of Leptin Transmembrane Signaling
Description: PUBLIC HEALTH RELEVANCE: Leptin signaling is key to the regulation of mammalian energy homeostasis and body weight. Extracellular binding of leptin to its receptor results in the intracellular activation of Janus kinase 2 (JAK2) which, in turns, regulates a number of physiologically crucial signaling cascades. We propose to apply molecular electron microscopy techniques to characterize the structure of the signaling complex between leptin, its receptor, and JAK2. The elucidation of this architecture will provide a mechanistic understanding of JAK2 activation via extracellular receptor engagement by leptin. Since deficient leptin signaling is associated with severe pathologies, such as obesity and diabetes, this knowledge will be ultimately used for the design of therapeutic strategies that are based on targeting the leptin receptor complex.
Funder: National Institutes of Health
Amount: $106,300
Funding type: research
Funder scheme: R01
Start date: 2017-08-01
End date: 2018-07-31
Investigator: GEORGIOS SKINIOTIS
Institution: STANFORD UNIVERSITY
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 18
Funder award ID: 7r01dk090165-08
OpenAlex ID: G5216631835